Nawalaniec James T, Landino Samantha M, O Jane M, Miller Cynthia L, Dehnadi Abbas, Hanekamp Isabel, Muoio Jayne Marie, Winter Casey, Hays Nicole, Allan James S, Madsen Joren C
Department of Surgery, Massachusetts General Hospital, Boston, MA, USA.
Center for Transplantation Sciences, Massachusetts General Hospital, Boston, MA, USA.
Sci Rep. 2024 Dec 30;14(1):31930. doi: 10.1038/s41598-024-83378-4.
The thymus is a rich source of regulatory T cells and plays a role in self-tolerance. Therefore, transplantation of a vascularized donor thymus may facilitate the induction of tolerance in recipients of a cotransplanted heart allograft. To investigate this hypothesis, we developed a new technique to procure the heart and thymus en bloc from juvenile donors and transplant the composite allograft into thymectomized recipients. Thymic function was monitored by serial biopsy and flow cytometry of peripheral blood. Heart-thymus en bloc transplantation resulted in immediate revascularization of the heart and donor thymus with maintenance of normal thymic architecture, even in biopsies taken months after transplantation. Heart-thymus en bloc transplantation requires minimal modification to current heart procurement techniques. Here, we describe the details of the preparation, procurement, transplantation, and postoperative monitoring for this model, with the intention that this technique could be implemented by other investigators to study the effects of heart and thymus cotransplantation. This method could ultimately offer a new approach to tolerance induction in children.
胸腺是调节性T细胞的丰富来源,在自身耐受中发挥作用。因此,移植带血管的供体胸腺可能有助于在同时移植心脏同种异体移植物的受者中诱导耐受。为了研究这一假设,我们开发了一种新技术,从幼年供体中整块获取心脏和胸腺,并将复合移植物移植到胸腺切除的受者体内。通过连续活检和外周血流式细胞术监测胸腺功能。心脏-胸腺整块移植导致心脏和供体胸腺立即再血管化,并维持正常的胸腺结构,即使在移植数月后的活检中也是如此。心脏-胸腺整块移植对当前的心脏获取技术只需进行最小程度的修改。在此,我们描述了该模型的制备、获取、移植及术后监测的细节,目的是其他研究人员能够采用该技术来研究心脏和胸腺联合移植的效果。该方法最终可能为儿童耐受诱导提供一种新途径。